General methods for enriching aldoses with oxygen isotopes

Synthetic methods are described for enriching 4-, 5-, and 6-carbon aldoses with oxygen isotopes. The general approach includes exchange between H2(1)8O and the aldehyde group of an aldose, exchange of O-1 onto C-2 of both of the 2-epimeric aldoses formed by molybdate-resin epimerization, and chain extension using cyanide addition. These methods make possible the production of all 16 aldohexoses enriched at 5 of the 6 oxygen atoms, all 8 aldopentoses enriched at 4 of the 5 oxygen atoms, and the four aldotetroses enriched at 2 of the 4 oxygen atoms. The general applicability of these methods is illustrated by the synthesis of a group of 22 different, 18O-enriched, biologically important D-aldoses having 4, 5, and 6 carbon atoms. The group includes D-[1-, 2-, 3-, 4-, O]glucose, D-[1-, 2-, 3-, 4-, and 6-18O]mannose, D-[1-, 2-, 3-, and 5-18O]arabinose, D-[1- abd 2- 18O] erythorose, and D-[1- and 2-18O]threose. The g.l.c.-m.s. characterization of these sugars with respect to the position and degree of 18O-enrichment is reported. The potential of the methods for producing aldoses having oxygen labels at multiple positions, or aldoses labeled simultaneously with oxygen, hydrogen, and carbon isotopes is discussed.